Carsalam (2H-1,3-benzoxazine-2,4(3H)-dione) is known in the art as an analgesic (see Merck Index, 12th edition, #1915).
Alkylated salicylamides, such as those disclosed in U.S. Pat. Nos. 5,650,386, 5,773,647, and 5,866,536, have been found to be highly effective as delivery agents for active agents, particularly for oral administration of active agents. Typically, these alkylated salicylamides are prepared by modifying an amino acid or an ester thereof. For example, these alkylated salicylamides may be prepared by acylation of an amino acid or an ester thereof with agents having a leaving group, such as a halogen, carbonyl group, or sulfonyl group, and an appropriate radical to yield the desired modification in the final product. See, for example, U.S. Pat. No. 5,650,386.
International Publication No. WO 00/46182 discloses a method for preparing an alkylated salicylamide by alkylating a protected/activated salicylamide and deprotecting and deactivating the protected/activated salicylamide. The alkylating agent may be, for example, ethyl 10-bromo-decanoate and ethyl 8-bromo-octanoate.
Alternate methods of producing alkylated salicylamides would be useful, especially where raw materials are expensive, yields are low, and reaction conditions are difficult.
Therefore, there is a need for simpler and less expensive methods of preparing alkylated salicylamides.